Research & Scholarship

Current Research and Scholarly Interests

My clinical and laboratory research activities are currently focused on developing new and sensitive means for detecting the onset of cerebral ischemia using both non-invasive electrophysiological and non-invasive optical techniques. The goal of this research is to provide new monitoring techniques to guide the clinical management of patients in which cerebral perfusion or other critical organ perfusion may be compromised.

Additional laboratory research activities are focused on developing an understanding of the mechanisms which underlie differential nerve block, and on identifying the sites of local anesthetic and opiate action within the spinal cord. The objective is to enable clinicians to provide regional analgesia without the many unwanted side effects of opiates and conventional local anesthetics. Achieving this goal could substantially improve pain management techniques and the practice of regional anesthesia.

Journal Articles

Abstract

During deep brain stimulation implant surgery, microelectrode recordings are used to map the location of targeted neurons. The effects produced by propofol or remifentanil on discharge activity of subthalamic neurons were studied intraoperatively to determine whether they alter neuronal activity.Microelectrode recordings from 11 neurons, each from individual patients, were discriminated and analyzed before and after administration of either propofol or remifentanil. Subthalamic neurons in rat brain slices were recorded in patch-clamp to investigate cellular level effects.Neurons discharged at 42 ± 9 spikes/s (mean ± SD) and showed a common pattern of inhibition that lasted 4.3 ms. Unique discharge profiles were evident for each neuron, seen using joint-interval analysis. Propofol (intravenous bolus 0.3 mg/kg) produced sedation, with minor effects on discharge activity (less than 2.0% change in frequency). A prolongation of recurrent inhibition was evident from joint-interval analysis, and propofol's effect peaked within 2 min, with recovery evident at 10 min. Subthalamic neurons recorded in rat brain slices exhibited inhibitory synaptic currents that were prolonged by propofol (155%) but appeared to lack tonic inhibitory currents. Propofol did not alter membrane potential, membrane resistance, current-evoked discharge, or holding current during voltage clamp. Remifentanil (0.05 mg/kg) had little effect on overall subthalamic neuron discharge activity and did not prolong recurrent inhibition.These results help to characterize the circuit properties and feedback inhibition of subthalamic neurons and demonstrate that both propofol and remifentanil produce only minor alterations of subthalamic neuron discharge activity that should not interfere with deep brain stimulation implant surgery.

Abstract

Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage.The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function.There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038).In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Abstract

In anesthesia and critical care, invasive arterial blood pressure monitoring is the gold standard against which other methods of monitoring are compared. In this assessment of the Philips MP90 monitor, the objective was to determine whether or not oscillometric measurements were within the accuracy standards set by the Association for the Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society (BHS). Three hundred and one invasive and noninvasive paired measurements were obtained from eleven adult patients on the neurosurgical service at Stanford University Medical Center. Bland-Altman plots were created to assess agreement between the two measurement systems. Paired correlation analysis, bias and precision calculations were performed. Oscillometric blood pressure measurements correlated with arterial measurements yielding Pearson r values of 0.68, 0.67 and 0.62 for systolic, diastolic and mean pressures, respectively (P < 0.01.) Mean differences with 95% confidence intervals were -3.8 mmHg +/- 13.6, -2.4 mmHg +/- 10.0, and 4.0 mmHg +/- 13.1 for systolic, diastolic and mean pressures, respectively. The mean difference for these measurements was

Abstract

Activating clotting time (ACT) is a point-of-care, blood clotting test used to monitor anticoagulation. Recently, institutional requirements have required that ACT testing be completed outside the operating room with trained, certified personnel other than anesthesia staff. For this reason, in this study, we looked at whether a delay in processing an ACT makes a significant difference to the ACT results. Twenty patients between 18 and 65 years of age consented to the study, each undergoing non-cardiac surgery, with no intraoperative administration of heparin. The study was approved by our Institutional Review Board. A blood sample was taken from the patient's arterial line in the operating room. Immediately afterward, 1 mL was placed into each of two ACT cartridges and the measurement was done in a Medtronic ACT2 machine. The first ACT value was 126.9 +/- 14.5 seconds. The ACT value at approximately 30 minutes was 108.3 +/- 20.3 seconds (p < .0001). The time between the first and last measurements was 29.4 +/- 3.0 minutes. The results suggest that the ACT values decrease over time between sampling all measurements. At approximately 30 minutes, the ACT values average 15% less than the control measurements. Therefore, it would seem prudent to determine ACT values immediately in the operating room without any delay, using point-of-care testing.

Abstract

Subarachnoid hemorrhage and surgical obliteration of ruptured intracranial aneurysms are frequently associated with neurological and neuropsychological abnormalities. We reported that intraoperative cooling did not improve neurological outcome in good-grade surgical subarachnoid hemorrhage patients, as assessed by the Glasgow Outcome Scale score or other neurological and functional measures (National Institutes of Health Stroke Scale, Rankin Disability Scale, Barthel Activities of Daily Living). We now report the results of neuropsychological testing in these patients.A total of 1,001 patients who bled < or = 14 days before surgery were randomly assigned to intraoperative hypothermia (t = 33 degrees C) or normothermia (37 degrees C). Outcome was assessed approximately 3 months after surgery. Patients underwent the Benton Visual Retention, Controlled Oral Word Association, Rey-Osterrieth Complex Figure, Grooved Pegboard, and the Trail Making tests. T-scores for each test were calculated from normative data. T-scores were averaged to calculate a Composite Score. A test result (or the Composite Score) was considered "impaired" if the T-score was two or more standard deviations below the norm. A Mini-Mental State Examination was also performed.Neurological outcome data were available in 1,000 patients. Sixty-one patients died. Of the 939 survivors, 873 completed 3 or more tests (exclusive of the Mini-Mental State Examination). Patients with poor neurological outcomes were less likely to complete testing; only 3.9% of Good Outcome (Glasgow Outcome Scale score = 1) patients were untested, compared with 38.6% of patients with Glasgow Outcome Scale scores of 3 and 4. There were no prerandomization demographic differences between the two treatment groups. For hypothermic patients, 16.8% were impaired from their Composite Score versus 20.0% of patients in the normothermic group (p = 0.317). For patients in the hypothermic group, 54.5% were impaired on at least one test, compared with 55.5% of patients in the normothermic group (p = 0.865). Similar results were seen in patients with baseline WFNS scores = I. Mini-Mental State Examination scores in the hypothermic and normothermic groups were 27.4 +/- 3.8 and 26.8 +/- 4.5, respectively.This is the largest prospective evaluation of neuropsychological function after subarachnoid hemorrhage to date. Testing was completed in a high fraction of patients, demonstrating the feasibility of such testing in a large trial. However, the frequent inability to complete testing in poor-outcome patients suggests that testing may be best used to refine outcome assessments in good-grade patients. Many patients showed impairment on at least one test, with global impairment present in 17 to 20% of patients (18-21% of survivors). This was true even among the patients with the best preoperative condition (WFNS = 1). There was no difference in the incidence of impairment between hypothermic and normothermic groups.

Abstract

Surgery for intracranial aneurysm often results in postoperative neurologic deficits. We conducted a randomized trial at 30 centers to determine whether intraoperative cooling during open craniotomy would improve the outcome among patients with acute aneurysmal subarachnoid hemorrhage.A total of 1001 patients with a preoperative World Federation of Neurological Surgeons score of I, II, or III ("good-grade patients"), who had had a subarachnoid hemorrhage no more than 14 days before planned surgical aneurysm clipping, were randomly assigned to intraoperative hypothermia (target temperature, 33 degrees C, with the use of surface cooling techniques) or normothermia (target temperature, 36.5 degrees C). Patients were followed closely postoperatively and examined approximately 90 days after surgery, at which time a Glasgow Outcome Score was assigned.There were no significant differences between the group assigned to intraoperative hypothermia and the group assigned to normothermia in the duration of stay in the intensive care unit, the total length of hospitalization, the rates of death at follow-up (6 percent in both groups), or the destination at discharge (home or another hospital, among surviving patients). At the final follow-up, 329 of 499 patients in the hypothermia group had a Glasgow Outcome Score of 1 (good outcome), as compared with 314 of 501 patients in the normothermia group (66 percent vs. 63 percent; odds ratio, 1.14; 95 percent confidence interval, 0.88 to 1.48; P=0.32). Postoperative bacteremia was more common in the hypothermia group than in the normothermia group (5 percent vs. 3 percent, P=0.05).Intraoperative hypothermia did not improve the neurologic outcome after craniotomy among good-grade patients with aneurysmal subarachnoid hemorrhage.

Abstract

It is common practice to hyperextend the wrist to facilitate insertion of a radial intra-arterial catheter. This position may be maintained for prolonged periods. Although there has been much discussion about optimal patient management to protect the ulnar nerve and brachial plexus, little attention has been paid to the median nerve during wrist hyperextension. The authors report the effects of wrist hyperextension on conduction in the median nerve.Median nerve conduction was studied in 12 awake, healthy volunteers using standard nerve conduction tests consisting of the measurement of compound sensory and motor action potentials, as well as their amplitudes and latencies. With the contralateral hand as a control, the right wrist was placed in hyperextension (angled between 65 and 80 degrees), and compound action potentials were recorded to determine the onset and magnitude of effects. Subsequently, the hand was released from hyperextension and recovery was recorded.In 83% of subjects, hyperextension resulted in a significant decrease in compound sensory action potential amplitudes, sufficient to qualify as conduction block (16.6% of baseline). The average time to conduction block was 43 +/- 13.2 min. All subjects who manifested conduction block showed marked improvement 5 min after release from hyperextension.Wrist hyperextension for arterial line placement and stabilization is likely to result in profound impairment of median nerve function. Although the effects were transient in this study, the results suggest that prolonged hyperextension may be associated with significant changes in median nerve conduction. To minimize the chance for nerve injury, the authors recommend that wrists be returned promptly to the neutral position following arterial line placement.

Abstract

The inadvertent intravascular injection of a local anesthetic during epidural anesthesia is an uncommon but potentially serious complication. Epinephrine, the most commonly used marker, does not provide sufficient sensitivity to exclude intravascular injection in all patient populations. The dye indocyanine green (ICG) has been proposed as an alternative marker. It has been demonstrated that ICG could be used to detect intravascular injections with a simple transcutaneous spectrophotometric technique. Although the safety of intravenous ICG is well documented, its neurotoxic potential requires careful study given the probability of inadvertent intrathecal injection during test injections used to verify epidural catheter placement.In this study, the authors investigated the neurophysiologic effects of clinically relevant concentrations of ICG (range, 28.6-286 microm) on single myelinated and unmyelinated dorsal root axons in rats by measuring effects on impulse generation and conduction.In contrast to the apparent absence of toxicity when injected intravenously, ICG applied to intact dorsal roots at concentrations likely to be encountered with an epidural test dose produced long-lasting conduction block (21 of 26 axons) or spontaneous bursting activity (7 of 26 axons) in myelinated and unmyelinated dorsal root axons.Given this apparent neurotoxicity, ICG should not be used when intrathecal or nerve root injection is possible.

Abstract

The goal of this study was to determine the effect of hydrocephalus on cerebrospinal fluid (CSF) production rates in patients with acute and chronic hydrocephalus.The authors studied CSF production both in patients presenting with acute and chronic hydrocephalus, and patients with Parkinson disease (PD) of a similar mean age, whose CSF production was known to be normal. A modification of the Masserman method was used to measure CSF production through a ventricular catheter. The CSF production rates (means +/- standard deviations) in the three groups were then compared. The patients with PD had a mean CSF production rate of 0.42 +/- 0.13 ml/minute; this value lies within the normal range measured using this technique. Patients with acute hydrocephalus had a similar CSF production rate of 0.4 +/- 0.13 ml/minute, whereas patients with chronic hydrocephalus had a significantly decreased mean CSF production rate of 0.25 +/- 0.08 ml/minute.The authors postulate that chronic increased intracranial pressure causes downregulation of CSF production.

Abstract

Cerebral ischemia and protection is a large field, so for the purposes of this review, which focuses on results published in the last 9 months, we have chosen to discuss a few aspects of ischemia in which our understanding has advanced significantly in this period of time. Recent progress in the clinical use of hypothermia for neurological protection as well as laboratory progress on the role of stress proteins, estrogen and a few other potential adjuncts will be discussed.Two papers have now been published documenting improved neurological outcome in patients treated with hypothermia following cardiac arrest, both using randomized clinical trial designs. These reports and several laboratory studies identifying mechanisms of hypothermic brain protection are reviewed. In understanding the mechanisms underlying protection by estrogens, new results on both direct vascular effects and a demonstration that estrogens can reduce apoptosis are presented. The third area to be described is current progress in identifying mechanisms of stress protein protection from ischemia, in which new mechanisms have been identified with the demonstration of inhibition of several points in the cell death cascade. The remaining areas considered touch on the effects of approaches that reduce inflammation by blocking adhesion molecules, those that reduce free radical production and those that improve blood rheology.An important common theme in brain protection is reduction of cell death by blocking apoptosis or programmed cell death. While the use of hypothermia should now enter clinical practice, many areas of brain injury require further studies both to define injury mechanisms and to translate these understandings into clinically useful treatments to reduce ischemic brain injury.

Abstract

We present here a case of a common problem for the anesthesiologist, i.e., difficulty in placing a Laryngeal Mask Airway (LMA). One solution is the use of the Yodfat technique to facilitate placement of the LMA.

Abstract

To evaluate the production rate of CSF in patients with differing disease states.The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 +/- 4 years, mean +/- SD), nine with PD over age 60 (aged 69 +/- 6 years, mean +/- SD), and seven with dementia of the Alzheimer's type (AD) (aged 72 +/- 9 years, mean +/- SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL.These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 +/- 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 +/- 0.12 mL/minute, and in patients with AD the mean rate was 0.20 +/- 0.06 mL/minute.These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

Abstract

Rewarming victims of hypothermia such as divers or immersion victims, participants in winter sports and military operations, and surgical patients on cardiopulmonary bypass (CPB) may lead to vascular instability, multiorgan failure, shock, and even death. While the causes of these rewarming symptoms are unknown, they may be related to bacterial lipopolysaccharide (LPS) translocated from the intestines into the circulation due to splanchnic ischemia. We have determined LPS during the cooling (to 31.5 degrees-34.0 degrees C) and rewarming phases of hypothermic surgery in 11 patients at the Stanford University Medical Center. During rewarming, there was an LPS spike in 6/11, in one more patient there was an LPS spike during surgery but not during rewarming, and in 4/11 there was no rise in LPS, i.e., a temporary endotoxemia occurred in 7/11 (63.6%) patients, usually at the commencement of rewarming. All four patients with no LPS spike received dexamethasone for at least 7 days before surgery. We propose that hypothermia reduced splanchnic blood flow (BF), causing ischemic damage to the gut wall and translocation of LPS from the gut into the vascular space. Upon rewarming, splanchnic BF is restored, the translocated LPS transits from the splanchnic to the systemic circulations as a bolus, and the gut wall is healed. No sequelae occurred in these patients because of their adequately functioning immune systems. However, had they been immunocompromised, symptoms might have occurred. Rewarming of accident victims probably also incurs a similar risk of endotoxemia, and dexamethasone may have protected the gut wall. Further studies are indicated.

Abstract

The underlying mechanism of enhanced antinociceptive effects and increased susceptibility to local anesthetics during pregnancy is not known. Mechanical, hormonal, biochemical, and neural changes have been suggested. The authors measured the susceptibility of individual spinal root axons to bupivacaine during late pregnancy in rats and compared them with similar measurements in nonpregnant rats.Lumbar dorsal and ventral roots were excised from anesthetized pregnant and nonpregnant rats. Single-fiber dissection and recording techniques were used to isolate activity in individual axons. Supramaximal constant voltage stimuli were delivered to the distal end of the root. During in vitro perfusion, each root was exposed to increasing concentrations of bupivacaine, and the minimum blocking concentration (Cm) and the concentration that increased conduction latency by 50% (EC50) were measured.Myelinated and unmyelinated dorsal and ventral root axons of pregnant rats appeared to be less sensitive to steady-state conduction block and to the latency-increasing effects of bupivacaine than were equivalent axons from nonpregnant rats. Although when comparing specific axon types, only the difference in C-fibers was significant (Cm = 29.8 microM for pregnant and Cm = 22.1 microM for nonpregnant rats, P < 0.05; EC50 = 19.9 microM and 13.6 microM, respectively).In contrast to clinical expectations, the susceptibility to bupivacaine conduction block in individual dorsal and ventral root axons during late pregnancy in rats was not greater in pregnant animals. Pregnancy-related changes in diffusion barriers and activation of endogenous analgesic systems without changes in the electrophysiologic properties of spinal root axons are suggested as possible explanations for the discrepancy between clinical and experimental observations.

A comparison of the local anesthetic effects of meperidine, fentanyl, and sufentanil on dorsal root axonsANESTHESIA AND ANALGESIAJaffe, R. A., Rowe, M. A.1996; 83 (4): 776-781

Abstract

The local anesthetic effects of opioids have been demonstrated in both clinical and laboratory studies. Clinically, both meperidine and sufentanil can produce segmental sensory anesthesia. However, previous studies of the effects of opioids on nerve conduction have all made use of peripheral nerve preparations and yielded conflicting results. In the present study we describe the local anesthetic effects of phenylpiperidine opioids on individual dorsal root axons, the probable target for intrathecal local anesthetics. Dorsal roots were removed from anesthetized adult male rats and maintained in vitro. Standard single fiber recording techniques were used to isolate activity in the individual axons. Drug exposure was accomplished by perfusing the isolated dorsal root with an artificial cerebrospinal fluid containing the study drug at a clinically relevant concentration. Steady-state drug effects were measured after 15-30 min of exposure and compared to control measurements in the same preparation. Meperidine (705 microM) blocked conduction in 61.5% of 39 myelinated and unmyelinated axons, and significantly reduced conduction velocity in the remaining unblocked axons. These effects were not naloxone reversible. Fentanyl (0.6 microM and 3 microM) and sufentanil (1.04 microM) failed to affect the nerve conduction in any dorsal root axon. The discrepancy between laboratory and clinical observations is discussed. We suggest that the site of conduction block may occur at the proximal end of the dorsal root as it passes through the dorsal root entry zone, an anatomically unique segment of the primary sensory pathway with decreased conduction safety for action potential propagation.

Abstract

Clinically, differential block is manifested by the loss of small fiber mediated sensation (e.g., temperature) two or more dermatomes beyond the sensory limit for large fiber mediated sensations. These observations support the belief that sensitivity to local anesthetics is inversely proportional to axon diameter. This study reports the first measurements of differential sensitivity to lidocaine in individual myelinated and unmyelinated mammalian dorsal root axons.Lumbar dorsal roots and vagus nerves were isolated from anesthetized adult rats and maintained in vitro in a perfusion/recording chamber at 37 +/- 0.3 degrees C. Using single fiber techniques, evoked action potentials in individual myelinated and unmyelinated axons were digitized and recorded for subsequent analysis. Axons were exposed to lidocaine at 150, 260, or 520 microM. Sensitivity to local anesthetic was assessed by measuring the incidence of conduction block and the magnitude of conduction velocity slowing under steady-state conditions.Data were obtained from 77 dorsal root axons and 41 vagal axons. The estimated steady-state EC50 lidocaine concentration for myelinated dorsal root axons (232 microM) was comparable to that for unmyelinated axons (228 microM). Similarly, the incidence of conduction block was not significantly different among dorsal root axon groups. However, unmyelinated dorsal root axons were significantly less sensitive to the conduction velocity slowing effect of lidocaine than their myelinated counterparts (P < 0.01). The incidence of conduction block in short (mean length 13.5 mm) dorsal root axons was not significantly different from that in long (mean length 22.4 mm) axons. Compared with dorsal root axons, the estimated EC50s for vagal myelinated and unmyelinated axons (345 and 285 microM, respectively), while lower were not significantly different. However, the incidence of conduction block at 260 microM lidocaine was significantly lower (16.7% vs. 56.7%; P < 0.05) in vagal myelinated axons.Although no difference in sensitivity to the conduction blocking effects of lidocaine could be demonstrated among dorsal root axons, myelinated axons were more sensitive to the conduction velocity slowing effects of lidocaine. This differential effect cannot explain clinical observations of differential nerve block. Differential sensory block with lidocaine may depend on factors (e.g., physiologic function) related only indirectly to individual axon conduction velocity (diameter).

Abstract

The object of this study, using transesophageal echocardiography (TEE) in anesthetized patients, was to investigate the occurrence of venous air embolism (VAE) when air is injected into the epidural space.Six patients between the ages of 18 and 50 years (ASA I-II) undergoing general anesthesia in a supine position for nonthoracic surgical procedures were studied. Prior to general anesthesia, an epidural catheter was placed into the epidural space using a Tuohy needle and a standard saline loss-of-resistance technique. Following verification of proper catheter placement, general anesthesia was induced and the trachea intubated. Thereafter, a TEE probe was inserted into the esophagus. After a 10-minute control period, and during continuous TEE videotape recording, 5 mL of air was rapidly injected into the epidural space through the epidural catheter. This was followed 10 minutes later by the epidural injection of 5 mL of room-temperature preservative-free saline. Microbubble echo targets were quantified in a range from 0 to 4+.Venous air microbubble emboli appeared in the circulation within 15 seconds after injecting either air or saline into the epidural space.No evidence of clinically significant VAE was seen in any patient. The results suggest that drugs injected into the epidural space may have unexpectedly easy access to the venous circulation with a potential to produce unwanted systemic effects. Clinicians should be alert to the possibility that local anesthetics, or any other drug placed epidurally, may rapidly enter the systemic circulation even without the intravenous placement of an epidural catheter.

Abstract

Systemically administered local anesthetics are known to provide analgesia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In the present study, the effects of low (subblocking for nerve conduction) concentrations of lidocaine on a spinal cord nociceptive potential were studied. Spinal cords were removed from neonatal rats and maintained in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Following a stabilization period (60-120 min) with control measurements, each preparation was exposed to a single concentration of lidocaine (30-60 min) then returned to control perfusate for recovery (60-120 min). Data were digitized and integrals computed for both monosynaptic and slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow-VRP. At lidocaine concentrations of 1-10 micrograms/ml (3.6-36 microM), the slow-VRP was reduced from 79% to 36% of control. Recovery to pre-exposure control levels was slow and sometimes not complete after 60-120 min in drug-free perfusate. The monosynaptic component of the VRP was unaffected by lidocaine at any concentration, suggesting that the depression of the slow-VRP cannot be attributed to simple conduction block. The addition of naloxone 0.1 microM to the perfusate had minimal effect on lidocaine-induced depression. Although resembling the selective effects of morphine, the antinociceptive effects of lidocaine do not appear to be primarily mediated through opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Five femora (four cadaveric and one plastic) were used to measure the intramedullary pressures simultaneously at two different locations along the proximal femur during the insertion of bone cement and the femoral component using modern cement technique. The pressures were monitored by transducers located at the midpoint of each femoral stem (P1), and just beyond the tip of the femoral stem proximal to a cement plug (P2). Transient increases in intramedullary pressure were noted during the initial compaction of the bone cement using a conventional device. However, during insertion of the femoral component, the pressures at P1 and P2 increased dramatically to peak pressures exceeding 2385 mm Hg at P1 and 3710 mm Hg at P2 respectively. These pressure elevations were not sustained; eight to 10 minutes after prosthesis insertion, the pressures decreased to below baseline levels in all five femora. This probably resulted from contraction of the cement during the curing phase. Transient elevations of intramedullary pressure to levels greater than 100 times capillary pressure are produced during hip replacement using modern cement technique. The highest pressures are generated during insertion of the femoral component rather than during the cement compaction step. These findings suggest that the use of a cement compactor to improve intrusion of the cement into bone is probably unnecessary.

Abstract

This study was designed to evaluate intrathecal (IT) sufentanil for labor analgesia with respect to sensory changes, side effects, and fetal heart rate (FHR) changes. In Phase I of the study, data regarding duration of analgesia and hemodynamic changes were obtained retrospectively from the labor and anesthetic records of 90 patients who had received IT sufentanil, 10 micrograms in 1 mL of saline, during active labor. In Phase II, an additional 18 parturients who received similar treatment were studied prospectively to document sensory, motor, and hemodynamic changes, as well as the incidence of side effects. In Phase I, analgesia occurred rapidly and lasted 124 +/- 68 min (SD); 19% of patients required no further analgesia before delivery. In Phase II, median time to onset of analgesia was 3 min (range 1-6 min) and mean duration of analgesia was 96 +/- 36 min. Decreased sensation to pinprick and cold occurred within 6 min extending from T4 to L4 (upper and lower median levels) in the majority of patients. All subjects requested additional analgesia within approximately 30 min of recession of sensory changes. Motor strength remained normal throughout. Hypotension (systolic blood pressure [BP] < or = 90 mm Hg or > 20% decrease in systolic BP) occurred in 14% and 11% of patients in Phase I and II, respectively. Perineal itching preceded analgesia in 95% of patients and all subjects experienced mild sedation. FHR changes occurred in 15% of cases but were not associated with adverse neonatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.

Abstract

Intraoperative transesophageal echocardiography was used to study the incidence of flow-patent foramen ovale in 33 normal, healthy patients (ASA physical status I) undergoing general anesthesia in the supine position for nonthoracic surgical procedures. Echocardiographic contrast was injected intravenously during mechanical ventilation in the presence of 0, 5, 10, 15, or 19 cm H2O positive end-expiratory pressure (PEEP). A final test was performed during the release of 19 cm H2O PEEP. The presence of a flow-patent foramen ovale was detected when the injected echo targets were observed crossing the interatrial septum from right to left. Most interesting, 3 of 33 patients developed a right-to-left shunt that was first detected with the steady application of 10 (1 patient) or 15 cm H2O PEEP (2 patients). In all three cases, the shunt flow was accentuated on the release of PEEP; however, no additional cases were detected using this respiratory maneuver. These cases represent the first demonstration of right-to-left interatrial shunting evoked as the result of the sustained application of PEEP. This study also revealed a lower than expected incidence of flow-patent foramen ovale (9%) when measured during general anesthesia and positive pressure ventilation with or without PEEP.

Abstract

Difficulties in removing the tracheal tube from the trachea are relatively uncommon. We report here a case of difficult extubation which was precipitated by pulling off the pilot balloon and valve assembly in order to deflate the cuff.

Abstract

Chronic exposure of animals to 60-Hz electric fields is known to affect the nervous system in a variety of subtle ways. The mechanism whereby these effects are produced remains unknown. One hypothesis is that the effects are a result of direct interaction between neuronal membranes and induced currents. Alternatively, the effects could be produced indirectly, as a result of sensory stimulation and the resulting low-level stress. To test these hypotheses, a system was developed to expose the surface of an anesthetized cat's paw to surface electric fields up to 600 kV/m while simultaneously measuring, in dorsal root fibers, afferent nerve impulses originating from various receptor types in the exposed paw. Of the 245 receptor units tested, comprising ten cutaneous receptor types, ten responded to the electric field with an increase in firing rate. The most sensitive receptor type was the rapidly adapting field receptor (RAF); eight of 20 (40%) were sensitive to the electric field, with thresholds as low as 160 kV/m. One of 35 rapidly adapting high-frequency receptors and one of 22 type T hair-follicle receptors were also sensitive to the electric field. Follow-up tests on the RAF receptors showed that hair removal reduced but did not eliminate the electric field sensitivity, suggesting that at least one other mechanism was involved in addition to stimulation via hair movement. The most likely mechanism is field-induced vibrations of the skin, since a further reduction in firing rate occurred following application of mineral oil to the depilated paw. Direct interaction with neuronal membranes is not supported by our evidence.

Abstract

Two independent series of experiments were performed on 114 male Sprague-Dawley-derived, albino rat pups, which represented 61 litters in experimental series I and 53 litters in experimental series II. Animals were exposed for 20 h/day from conception to testing (postnatal days 11-20) to a vertical, 65-kV/m, 60-Hz electric field or sham-exposed. Recordings of the visual-evoked response (VER) were obtained using a small silver ball electrode placed epidurally over the visual cortex. Visual stimuli consisted of 10-microseconds light flashes delivered at 0.2 Hz. Computer-averaged VERs were obtained and power spectral analyses (fast Fourier transform) were performed on the tapered (split cosine-bell window), averaged VERs. The expected age-related changes were clearly evident; however, a detailed analysis of VER component latencies, peak-to-peak amplitude, and power spectra failed to reveal any consistent, statistically significant effect of exposure to 60-Hz electric fields.

Abstract

Neuromuscular function in adult male rats was studied following 30 days of exposure to a 60-Hz electric field at 100 kV/m (unperturbed field strength). Isometric force transducers were attached to the tendons of the plantaris (predominantly fast twitch), and soleus (predominantly slow twitch) muscles in the urethan-anesthetized rat. Square-wave stimuli were delivered to the distal stump of the transected sciatic nerve. Several measurements were used to characterized neuromuscular function, including twitch characteristics, chronaxie, tetanic and posttetanic potentiation, and fatigue and recovery. The results from three independent series of experiments are reported. Only recovery from fatigue in slow-twitch muscles was consistently and significantly affected (enhanced) by electric-field exposure. This effect does not appear to be mediated by field-induced changes in either neuromuscular transmission, or in the contractile mechanism itself. It is suggested that the effect may be mediated secondary to an effect on mechanisms regulating muscle blood flow or metabolism.

Abstract

Several reports have suggested that the nervous system can be affected by exposure to electric fields and that these effects may have detrimental health consequences for the exposed organism. The purpose of this study was to investigate the effects of chronic (30-day) exposure of rats to a 60Hz, 100-kV/m electric field on synaptic transmission and peripheral-nerve function. One hundred forty-four rats, housed in individual polycarbonate cages were exposed to uniform, vertical, 60-Hz electric fields in a system free of corona discharge and ozone formation and in which the animals did not receive spark discharges or other shocks during exposure. Following 30 days of exposure to the electric field, superior cervical sympathetic ganglia, vagus and sciatic nerves were removed from rats anesthetized with urethan, placed in a temperature-controlled chamber, and superfused with a modified mammalian Ringer's solution equilibrated with 95% O2 and 5% CO2. Several measures and tests were used to characterize synaptic transmission and peripheral-nerve function. These included amplitude, area, and configuration of the postsynaptic or whole-nerve compound-action potential; conduction velocity; accommodation; refractory period; strength-duration curves; conditioning-test (C-T) response, frequency response; post-tetanic response; and high-frequency-induced fatigue. The results of a series of neurophysiologic tests and measurements indicate that only synaptic transmission is significantly and consistently affected by chronic (30-day) exposure to a 60-Hz, 100-kV/m electric field. Specifically, and increase in synaptic excitability was detected in replicated measurements of the C-T response ratio. In addition, there are trends in other data that can be interpreted to suggest a generalized increase in neuronal excitability in exposed animals.

Abstract

1 The effect of droperidol on the spontaneous activity of carotid body chemoreceptors and on their response to various stimuli was studied in 21 anaesthetized, paralyzed and artificially ventilated cats. Carotid body blood flow was controlled with a perfusion pump, and drugs were injected into the perfusion circuit. 2 In low doses, droperidol transiently increased the rate of spontaneous chemoreceptor activity, but in higher doses it depressed chemoreceptor activity after an initial stimulation. 3 Droperidol reduced or abolished the normal increase in chemoreceptor activity produced by stagnant asphyxia. This effect did not depend solely on the ability of droperidol to suppress spontaneously occurring impulses. Chemoreceptor responses to sodium cyanide, and to dopamine were also inhibited. 4 Dopamine antagonists other than droperidol were also studied for their effect on chemocreceptor activity. Chlorpromazine depressed spontaneous chemoreceptor activity and also reduced the chemoreceptor responses to sodium cyanide and dopamine, as did pimozide. The effects of these dopamine antagonists were much briefer and less marked than those of droperiodol. 5 Although the influence that we have shown droperidol to have on peripheral chemoreceptor activity has an uncertain basis, it may have important implications in human and veterinary medicine.

Abstract

1. We studied the passive and active electrical properties of the soma membrane of neurons in nodose ganglia removed from cats and rabbits and maintained in vitro. The ganglia were superfused at 37 degrees C with a solution formulated to approximate the extracellular fluid of each species. The solution was buffered to pH 7.34, continuously equilibrated with 95% O2 and 5% CO2, and contained dialyzed calf serum and glucose. We also examined these properties in nodose ganglion neurons in vivo. Intracellular recordings were obtained with glass micropipettes filled with either 3 M KCl or 5 M K acetate. 2. We determined mean values for a variety of passive and active electrophysiologic properties. Values obtained in vitro did not differ significantly from those obtained in vivo. Based on the passive electrical properties of the soma membrane, neurons in the nodose ganglion appear to be a uniform population, despite the different sensory modalities conveyed by the afferent fibers. 3. Cell bodies of neurons generated action potentials in response to impulses in their afferent fibers. Somatic spikes could be evoked by stimulation of either the supranodose or infranodose vagus nerve, and an inflection point could be seen on their rising phase. When the vagus nerve was stimulated at frequencies greater than 10-20 Hz, the generation of somatic spikes often became progressively delayed and then failed completely, leaving a smaller potential (IS spike) which was apparently generated in the initial complex. The afterhyperpolarization was associated only with the somatic spike. 4. Many neurons, both in vitro and in vivo, developed a persistent hyperpolarization when repetitive action potentials occurred in the soma. This hyperpolarization was apparent at frequencies as low as 1-2 Hz, persisted for up to 5 s after the occurrence of the last somatic spike, and sometimes caused failure of somatic spikes to be generated. 5. Neurons in both species differed in their responses to suprathreshold depolarization applied through the recording electrode. Some neurons produced a train of action potentials which lasted for the duration of the depolarizing pulse, the frequency of the train being related to the magnitude of depolarization. The trains were characterized by gradually decreasing spike amplitudes and increasing interspike intervals. Other neurons responded with only a single spike or brief burst of action potentials at the beginning of depolarization to threshold. 6. It is suggested that the adaptive properties of the soma membrane of a peripheral sensory neuron are similar to those of its sensory ending, and that electrophysiological studies of the soma membrane may provide an opportunity to examine mechanisms of receptor adaptation.

Abstract

Experiments were performed to determine the mechanism by which centrifugal impulses in the carotid sinus nerve (CSN) reduce the frequency of impulse traffic in afferent chemoreceptor fibers from the carotid body in cats. Recordings of chemoreceptor activity were made from single- or few-fiber preparations dissected off the CSN, while the remainder of the CSN was stimulated electrically to produce neurally induced inhibition of chemoreceptor activity. Various drugs were injected either intravenously or directly into the arterial blood supply to the carotid body. We found that catecholamines (dopamine, norepinephrine and epinephrine) inhibited spontaneous chemoreceptor activity, and that alpha adrenergic antagonists abolished both this inhibition and that produced by electrical stimulation of the CSN in the same preparation. Atropine, but not nicotinic antagonists of acetylcholine, consistently blocked neurally induced inhibition but not that produced by catecholamines. Muscarinic agonists had no effect on spontaneous chemoreceptor activity. We conclude that centrifugal activity in the CSN causes release of endogenous catecholamines in the carotid body, and that these catecholamines mediate neurally induced inhibition of chemoreceptor activity is due to the vasomotor effects of acetylcholine.

Abstract

The inhibitory effect of dopamine on carotid body chemoreceptors was studied in anesthetized cats to determine whether it was dependent on changes in blood flow in the vicinity of the receptors. The blood supply to the carotid body was isolated, and flow was controlled with a perfusion pump. Single- or few-fiber recordings were made from the peripheral end of the cut carotid sinus nerve in seven cats. The rate of discharge of 68 chemoreceptor strands increased when flow through the carotid body was stopped. This response was reduced or abolished by dopamine in animals ventilated with either room air (15 strands) or a gas mixture of 95% O2 and 5% CO2 (53 strands). These results suggest that dopamine exerts its inhibitory effect primarily through a direct action on the chemoreceptors rather than by a vasomotor effect in the carotid body.

Abstract

The dynamics of venous-arterial testosterone transfer in the pampiniform plexus of the rat have been studied using [3-H] testosterone in controlled perfusion in the pampiniform plexus isolated from its testicle in vivo. The rate of transfer of testosterone increased in direct proportion to the testosterone concentration in spermatic vein blood over the range 0-100 ng/ml. When the venous-arterial concentration gradient was reversed by infusing [14-C] testosterone into the spermatic artery proximal to the pampiniform plexus, the label was transferred from the artery to the adjacent spermatic vein. Transfer of [3-H] methoxy-inulin infused concomitantly with the [14-C] testosterone was relatively insignificant in either direction. The testosterone transfer rate generally increased with increasing blood flow over the range 0.01-0.36 ml/min. However, transfer rate became less dependent on blood flow at the high end of the range. A comparison of transfer rates from whole blood and dextran (6% in saline) each containing 24-27 ng [1,2-3-H] testosterone/ml and flowing at 0.36 ml/min for one hour resulted in a maximum of 6.1% transfer from blood and 46% transfer from dextran. Transfer from blood reached plateau levels in less than 10 min, whereas transfers from dextran peaked between 30 and 40 min. At lower rates testosterone transfer from dextran reached equilibration levels, whereas transfer from blood rarely exceeded 5% of spermatic venous levels. We concluded that venous-arterial steroid transfer in the pampiniform plexus behaves like a passive countercurrent diffusion system that is concentration limited, depending principally on the concentration gradient of diffusible steroid between the closely juxtaposed spermatic vein and artery.

Abstract

The effects of centrifugal activity in the carotid sinus nerve (CSN) on the intensity of formaldehyde-induced fluorescence of carotid body were examined in cat. Measurements of intensity were obtained from 21 to 56 sections of each carotid body with a microscope photometer attached to a fluorescence microscope. Comparisons were made between the two carotid bodies removed from each cat. In one series of experiments, one carotid body (CSN intact) served as control, while the experimental carotid body was on the side on which centrifugal activity was increased by electrical stimulation of the peripheral end of the cut CSN. In a second series, centrifugal CSN activity was increased by hypoxemia; one CSN was transected (control) and the other was left intact (experimental). In untreated cats, fluorescence intensity was significantly higher on the side with increased centrifugal CSN activity. In cats treated with either MK486, which inhibits conversion of L-DOPA to dopamine, or reserpine, increased centrifugal CSN activity caused a significant decrease in intensity of type I cells. These findings indicate that centrifugal discharges regulate, in part, the synthesis and release of catecholamines by type I cells of the carotid body.

Conference Proceedings

Abstract

Clinically, bupivacaine can provide excellent sensory anesthesia with minimal impairment of motor function. However, the mechanisms by which local anesthetics produce differential sensory-motor nerve block is still unknown. The primary site of action for spinal and epidural anesthetics is thought to be the intradural segment of the spinal root. To determine the differential susceptibility of single motor and sensory nerve fibers to local anesthetic conduction block, bupivacaine effects on individual dorsal root (DR) and ventral root (VR) axons were studied.Lumbar DRs and VRs were excised from anesthetized adult male rats. Single-fiber dissection and recording techniques were used to isolate activity in individual axons. Supramaximal constant-voltage stimuli at 0.3 Hz were delivered to the root. During in vitro perfusion, each root was exposed to increasing concentrations of bupivacaine, and the minimum blocking concentration (C(m)) and the concentration that increased conduction latency by 50% (latency EC50) were measured.Ventral root axons were significantly more sensitive to the steady-state conduction blocking effects of bupivacaine than were either myelinated or unmyelinated DR axons (DR-C(m), 32.4 microM; VR-C(m), 13.8 microM; P < 0.0001). In addition, VR axons were more susceptible to the latency-increasing effects of bupivacaine than were DR axons (DR-EC50 = 20.7 microM; VR-EC50 = 8.5 microM; P < 0.0001). Within axon groups, differential sensitivity as a function of conduction velocity (axon diameter), or length of nerve exposed to the anesthetic could not be demonstrated.In contrast to clinical expectations, low concentrations of bupivacaine preferentially block motor (VR) axons in the rat.